ArticleCell death discovery2023
Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 49 citations in OpenAlex.
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Review
- Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis.Journal of cellular physiology · 2026Article
- Resetting the immune setpoint of cold tumors through a ferroptosis-cGAS-STING amplification circuit.Journal of translational medicine · 2026Review
- Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration.Bioactive materials · 2026Article
- Ferroptosis in retinal pigment epithelial cells: Current status and future developments.Indian journal of ophthalmology · 2026Review
- Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- Ionizing radiation promotes lung injury by inducing ferroptosis-driven senescence in epithelial cells via NCOA4-mediated ferritinophagy.Redox biology · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- The Crosstalk Mechanisms Between Ferroptosis and Pyroptosis and Their Applications in Diseases: From Molecular Networks to Clinical Strategies.Journal of cellular and molecular medicine · 2026Review
- Insights Into Macrophage Ferroptosis: Implications for Atherosclerosis.Cell proliferation · 2026Review
- Mitochondrial Iron Handling and Lipid Peroxidation as Drivers of Ferroptosis.International journal of molecular sciences · 2026Review
- Mitochondrial homeostasis and aging: the mtDNA-cGAS-STING axis.Frontiers in immunology · 2026Review
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
- The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Targeting Aging and Diseases Associated with Ferroptosis and Senescence Through Modulation of Iron, Oxidative Stress and Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2025Review
- Interplay of cGAS-STING and ferroptosis: crosstalk, molecular mechanisms, and therapeutic prospects.Archives of toxicology · 2025Review
- PCBP2 Regulates p16Aging cell · 2025Article
- Phylloquinone Attenuates Oxygen-Glucose Deprivation-induced Neuronal Injury by Inhibiting Ferroptosis via the xCT/GPX4 Pathway.Neurochemical research · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.